Tumor-derived exosomal miR-425-5p and miR-135b-3p enhance colorectal cancer progression through immune suppression and vascular permeability promotion
Year: 2025
Type: article
Abstract: BACKGROUND Colorectal cancer (CRC) is a leading cause of cancer-related morbidity and mortality globally. Exosomal microRNAs (miRNAs) are known to modulate tumor progression by influencing immune responses and vascular dynamics. However, the roles of specific exosomal miRNAs, such as miR-425-5p and miR-135b-3p, in CRC remain unclear. AIM To explore the specific roles and underlying mechanisms of exosomal miR-425-5p and miR-135b-3p in CRC progression. METHODS Differentially expressed miRNAs were identified through microarray analysis of exosomes isolated from CRC tissues and adjacent normal mucosa. Functional roles of miR-425-5p and miR-135b-3p were evaluated in vitro using macrophage polarization, T cell differentiation, and vascular permeability assays, as well as in vivo tumor formation and metastasis experiments in nude mice. Validation experiments were performed using CRC cell lines (HCT116 and SW620). RESULTS Exosomal miR-425-5p and miR-135b-3p were significantly upregulated in CRC compared to normal tissues. Functional studies revealed that miR-425-5p promotes macrophage M2-like polarization and suppresses T cell proinflammatory responses, while miR-135b-3p enhances vascular permeability and angiogenesis. Inhibition of these miRNAs in CRC cell-derived exosomes significantly suppressed tumor growth and metastasis in nude mice, reprogramming the tumor microenvironment toward reduced angiogenesis and enhanced immune activation. Combined inhibition of both miRNAs resulted in the most pronounced effects. CONCLUSION Exosomal miR-425-5p and miR-135b-3p drive CRC progression by promoting immune suppression and vascular permeability. Their inhibition offers a promising strategy for modulating the tumor microenvironment and limiting CRC metastasis.
Authors: Chun-Zai Feng, Si-Quan Zhong, Shao-Wei Ye, Zheng Zheng, Hao Sun, Shi-Hai Zhou
Institution: Zhongshan People's Hospital
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: diamond
OpenAlex ID: W4411226077